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Circulation. 2018 Mar 6;137(10):1027-1038. doi: 10.1161/CIRCULATIONAHA.117.031431. Epub 2017 Nov 12.

Genetic Predisposition, Clinical Risk Factor Burden, and Lifetime Risk of Atrial Fibrillation.

Author information

1
Cardiovascular Research Center (L.-C.W., O.L.H., P.T.E., S.A.L.).
2
Massachusetts General Hospital, Boston. Program in Medical and Population Genetics, The Broad Institute of Harvard and MIT, Cambridge, MA (L.-C.W., O.L.H., S.H.C., P.T.E., S.A.L.).
3
Department of Biostatistics, Boston University School of Public Health, MA (S.R.P., M.G.L., B.W., L.T., K.L.L.).
4
Boston University and National Heart, Lung and Blood Institute's Framingham Heart Study, MA (S.R.P., M.G.L., L.T., L.S., H.L., K.L.L., E.J.B.).
5
Department of Medicine, Cardiology Division, University of Massachusetts Medical School, Worcester (D.D.M.).
6
Cardiovascular Research Center, Herlev and Gentofte University Hospital, Hellerup, Denmark (L.S.).
7
Department of Medicine, Sections of Computational Biomedicine (H.L.).
8
Cardiac Arrhythmia Service (P.T.E., S.A.L.).
9
Preventive Medicine and Cardiovascular Medicine (E.J.B.), Boston University School of Medicine, MA.
10
Cardiovascular Research Center (L.-C.W., O.L.H., P.T.E., S.A.L.) slubitz@mgh.harvard.edu.

Abstract

BACKGROUND:

The long-term probability of developing atrial fibrillation (AF) considering genetic predisposition and clinical risk factor burden is unknown.

METHODS:

We estimated the lifetime risk of AF in individuals from the community-based Framingham Heart Study. Polygenic risk for AF was derived using a score of ≈1000 AF-associated single-nucleotide polymorphisms. Clinical risk factor burden was calculated for each individual using a validated risk score for incident AF comprised of height, weight, systolic and diastolic blood pressure, current smoking status, antihypertensive medication use, diabetes mellitus, history of myocardial infarction, and history of heart failure. We estimated the lifetime risk of AF within tertiles of polygenic and clinical risk.

RESULTS:

Among 4606 participants without AF at 55 years of age, 580 developed incident AF (median follow-up, 9.4 years; 25th-75th percentile, 4.4-14.3 years). The lifetime risk of AF >55 years of age was 37.1% and was substantially influenced by both polygenic and clinical risk factor burden. Among individuals free of AF at 55 years of age, those in low-polygenic and clinical risk tertiles had a lifetime risk of AF of 22.3% (95% confidence interval, 15.4-9.1), whereas those in high-risk tertiles had a risk of 48.2% (95% confidence interval, 41.3-55.1). A lower clinical risk factor burden was associated with later AF onset after adjusting for genetic predisposition (P<0.001).

CONCLUSIONS:

In our community-based cohort, the lifetime risk of AF was 37%. Estimation of polygenic AF risk is feasible and together with clinical risk factor burden explains a substantial gradient in long-term AF risk.

KEYWORDS:

atrial fibrillation; epidemiology; genetics; lifetime risk; polygenic risk; risk factor; risk stratification

PMID:
29129827
PMCID:
PMC5840011
[Available on 2019-03-06]
DOI:
10.1161/CIRCULATIONAHA.117.031431

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